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Early life overfeeding impairs spatial memory performance by reducing microglial sensitivity to learning.

Simone N De Luca1, Ilvana Ziko1, Luba Sominsky1

  • 1School of Health and Biomedical Sciences, RMIT University, Melbourne, Vic., 3083, Australia.

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Early life overfeeding in rats leads to lasting obesity and impaired learning and memory, linked to microglial changes in the brain. This suggests early diet impacts long-term cognitive function.

Keywords:
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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Immunology

Background:

  • Obesity is linked to cognitive dysfunction, but the adult brain shows resistance to its effects.
  • Early-life overfeeding in rats causes lasting obesity and hypothalamic microglial priming.
  • Microglial hypersensitivity in memory regions may underlie cognitive deficits in overfed individuals.

Purpose of the Study:

  • To investigate if neonatal overfeeding induces microglial changes in memory-associated brain regions.
  • To determine if these microglial alterations result in cognitive deficits in rats.

Main Methods:

  • Wistar rat pups were assigned to small (overfed, n=4) or large (control, n=12) litters.
  • Microgliosis, cell proliferation, and neuron numbers were assessed in hippocampus and retrosplenial cortex.
  • Cognitive performance was evaluated using the radial arm maze and novel object recognition tests.

Main Results:

  • Neonatally overfed rats exhibited persistent microgliosis in the hippocampus from 14 days into adulthood.
  • Overfed rats showed poorer performance in memory tasks compared to controls.
  • Learning tasks in control rats reduced cell proliferation and neuron numbers, and suppressed microglia; overfed rats showed impaired learning sensitivity and less microglial suppression.

Conclusions:

  • Early-life overfeeding induces long-term cognitive impairments in learning and memory, involving microglial activation.
  • These findings suggest the early-life dietary environment plays a crucial role in long-term cognitive health.
  • The study provides a potential explanation for variability in cognitive dysfunction among obese individuals.